Biology of Cancer-Testis Antigens and Their Therapeutic Implications in Cancer
Abstract
:1. Introduction
2. Discovery of CTAs
3. CTA Biology in Carcinogenesis
3.1. CTAs in the Regulation of Transcriptional Programs Involved in Tumorigenesis
3.2. CTAs in Cell Division, Genomic Instability and the DNA Damage Response
3.3. Role of CTAs in the Evasion of Apoptosis
3.4. CTAs and Metastasis: Epithelial-to-Mesenchymal Transition
3.5. Preferential Expression of CTAs in Cancer Stem Cells (CSCs)
3.6. CTAs in Cancer Cell Energetics and Autophagy
3.7. CTAs and the Tumour Microenvironment
4. Regulation of CTAs
5. CTAs as Therapeutic Targets: Perspectives and Future Implications
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Therapy | NCT Number | Title | Cancer Type | Target CTA | Sponsor | Location |
---|---|---|---|---|---|---|
T-Cell | NCT05430555 | A Phase 1/2, First-in-Human, Open-Label, Two-Part Clinical Trial of TK-8001 in Patients With HLA-A*02:01 Genotype and Advanced-Stage/Metastatic MAGE-A1+ Solid Tumors | Advanced Solid tumours | MAGEA1 | T-knife GmbH | Berlin, Germany |
NCT03240861 | Genetically Engineered PBMC and PBSC Expressing NY-ESO-1 TCR After a Myeloablative Conditioning Regimen to Treat Patients With Advanced Cancer | Malignant Neoplasm/ Sarcoma | NY-ESO-1 | Jonsson Comprehensive Cancer Center | CA, USA | |
NCT04752358 | ADP-A2M4CD8 in HLA-A2+ Subjects With MAGE-A4 Positive Esophageal or Esophagogastric Junction Cancers (SURPASS-2) | Esophageal Cancer/ Esophagogastric Junction Cancer | MAGEA4 | Adaptimmune | UK | |
NCT04729543 | MAGE-C2 TCR T Cell Trial to Treat Melanoma and Head and Neck Cancer | Melanoma/ Head and Neck Cancer | MAGEC2 | Erasmus Medical Center | Rotterdam, Netherlands | |
NCT05296564 | Anti-NY-ESO-1 TCR-Gene Engineered Lymphocytes Given by Infusion to Patients With NY-ESO-1 -Expressing Metastatic Cancers | Metastaic solid tumours | NY-ESO-1 | Hadassah Medical Organization | Jerusalem, Israel | |
NCT04044859 | ADP-A2M4CD8 as Monotherapy or in Combination With Either Nivolumab or Pembrolizumab in HLA-A2+ Subjects With MAGE-A4 Positive Tumors (SURPASS) | Multiple Solid Tumors | MAGEA4 | Adaptimmune | UK | |
NCT03652545 | Multi-antigen T Cell Infusion Against Neuro-oncologic Disease | Brain Tumor | WT1, PRAME | Catherine Bollard | WA, USA | |
NCT04884282 | Efficacy of Tedopi Plus Docetaxel or Tedopi Plus Nivolumab as Second-line Therapy in Metastatic Non-small-cell Lung Cancer Progressing After First-line Chemo-immunotherapy (Combi-TED) | Metastatic Non-Small Cell Lung Cancer | MAGE2/3 | Fondazione Ricerca Traslazionale | Roma, Italy | |
NCT05134740 | (TAA)-Specific Cytotoxic T-Lymphocytes to Pediatric Patients With Lymphomas (pediTACTAL). | Hodgkins Lymphoma, Non Hodgkins Lymphoma | NY-ESO-1, MAGEA4, PRAME, SSX. | Baylor College of Medicine | TX, USA | |
NCT05620693 | Study of NY-ESO-1 TCR-T in Advanced Soft Tissue Sarcoma | Advanced Soft-tissue Sarcoma | NY-ESO-1 | Shenzhen University General Hospital | Shenzhen, China | |
NCT03462316 | NY-ESO-1-specific T Cell Receptor (TCR) T Cell in Sarcoma | Bone Sarcoma, Soft Tissue Sarcoma | NY-ESO-1 | Sun Yat-sen University | Guangzhou, China | |
NCT05549921 | Phase II Study of TAEST16001 in Soft Tissue Sarcoma | Soft Tissue Sarcoma | NY-ESO-1 | Sun Yat-sen University | Shenzhen, China | |
NCT02494167 | Administration of Donor Multi TAA-Specific T Cells for AML or MDS (ADSPAM) | Acute Myeloid Leukemia, Myelodysplastic Syndrome | NY-ESO-1 | Baylor College of Medicine | TX, USA | |
NCT04044768 | Spearhead 1 Study in Subjects With Advanced Synovial Sarcoma or Myxoid/Round Cell Liposarcoma | Synovial Sarcoma, Myxoid Liposarcoma | MAGEA4 | Adaptimmune | UK | |
NCT01946373 | T Cell Transfer With or Without Dendritic Cell Vaccination in Patients With Melanoma | Melanoma | NY-ESO-1 | Karolinska University Hospital | Slona, Sweden | |
NCT03686124 | ACTengine® IMA203/IMA203CD8 as Monotherapy or in Combination With Nivolumab in Recurrent and/or Refractory Solid Tumors | Solid Tumor, Recurrent Solid Tumors, Refractory Solid Tumors | PRAME | Immatics US, Inc. | TX, USA | |
NCT05035407 | T Cell Receptor Gene Therapy Targeting KK-LC-1 for Gastric, Breast, Cervical, Lung and Other KK-LC-1 Positive Epithelial Cancers | Gastric, Breast, Cervical, Lung and Other KK-LC-1 Positive Epithelial Cancers | KK-LC-1 | National Cancer Institute (NCI) | MD, USA | |
Vaccine | NCT04908111 | A Trial of ChAdOx1 and MVA Vaccines Against MAGE-A3 and NY-ESO-1 | Non-small Cell Lung Cancer | MAGEA3, NY-ESO-1 | Cancer Research UK | London, UK |
NCT04739527 | Phase 1 Study to Evaluate the Safety, Feasibility and Immunogenicity of an Allogeneic, Cell-based Vaccine (DCP-001) in High Grade Serous Ovarian Cancer Patients After Primary Treatment | Ovarian Cancer | WT1, PRAME | University Medical Center Groningen | Groningen, Netherland | |
NCT03970746 | Safety, Immunogenicity and Preliminary Clinical Activity Study of PDC*lung01 Cancer Vaccine in NSCLC | Non Small Cell Lung Cancer | NY-ESO-1, MAGEA3, MAGEA4, Multi-MAGE | PDC*line Pharma SAS | Brussels, Belgium | |
NCT04751786 | Dose Escalation Study of Immunomodulatory Nanoparticles | Advanced Solid Tumor | NY-ESO-1 | Radboud University Medical Center | Nijmegen, Netherlands | |
Others | NCT03973333 | Safety and Efficacy of IMC-C103C as Monotherapy and in Combination With Atezolizumab | Select Advanced Solid Tumors | MAGEA4 | Immunocore Ltd. | Oxfordshire, UK |
NCT04262466 | Safety and Efficacy of IMC-F106C as a Single Agent and in Combination With Checkpoint Inhibitors | Select Advanced Solid Tumors | PRAME | Immunocore Ltd. | Oxfordshire, UK | |
NCT05251714 | CFI-402257, a Potent and Selective TTK Inhibitor, in Solid Tumors and With Fulvestrant in Breast Cancer | Advanced Solid Tumors, Breast Cancer | TTK | Treadwell Therapeutics, Inc. | NY, USA |
Therapy | NCT Number | Title | Cancer Type | Target CTA | Sponsor | Location |
---|---|---|---|---|---|---|
T-Cell | NCT03139370 | Safety and Efficacy of MAGE-A3/A6 T Cell Receptor Engineered T Cells (KITE-718) in HLA-DPB1*04:01 Positive Adults With Advanced Cancers | Multiple Solid Tumors | MAGEA3/A6 | Kite, A Gilead Company | CA, USA |
NCT03132922 | MAGE-A4ᶜ¹º³²T for Multi-Tumor | Solid tumours | MAGEA4 | Adaptimmune | UK | |
NCT02869217 | Study of TBI-1301 (NY-ESO-1 Specific TCR Gene Transduced Autologous T Lymphocytes) in Patients With Solid Tumors | NY-ESO-1 Expressing Solid Tumors | NY-ESO-1 | University Health Network, Toronto | Toronto, Canada | |
NCT03093350 | TACTIC - TAA Specific Cytotoxic T Lymphocytes in Patients With Breast Cancer | Breast Cancer | NY-ESO-1, MAGEA4, PRAME, SSX2 | Baylor College of Medicine | TX, USA | |
NCT02650986 | Gene-Modified T Cells With or Without Decitabine in Treating Patients With Advanced Malignancies Expressing NY-ESO-1 | Advanced Solid tumours | NY-ESO-1 | Roswell Park Cancer Institute | NY, USA | |
NCT03192462 | TAA Specific Cytotoxic T Lymphocytes in Patients With Pancreatic Cancer | Pancreatic Cancer | NY-ESO-1, MAGEA4, PRAME, SSX2 | Baylor College of Medicine | TX, USA | |
NCT03691376 | Genetically Engineered Cells (NY-ESO-1 TCR Engineered T Cells and HSCs) After Melphalan Conditioning Regimen in Treating Patients With Recurrent or Refractory Ovarian, Fallopian Tube, or Primary Peritoneal Cancer | Recurrent or Refractory Ovarian, Fallopian Tube, or Primary Peritoneal Cancer | NY-ESO-1 | Roswell Park Cancer Institute | NY, USA | |
NCT04526509 | Master Protocol to Assess Safety and Dose of First Time in Human Next Generation Engineered T Cells in NY-ESO-1 and/or LAGE-1a Positive Advanced Solid Tumors | Neoplasms | NY-ESO-1and LAGE-1a | GlaxoSmithKline | London, UK | |
NCT03967223 | Master Protocol to Assess the Safety and Antitumor Activity of Genetically Engineered T Cells in NY-ESO-1 and/or LAGE-1a Positive Solid Tumors | Neoplasms | NY-ESO-1 | GlaxoSmithKline | London, UK | |
NCT03017131 | Genetically Modified T Cells and Decitabine in Treating Patients With Recurrent or Refractory Ovarian, Primary Peritoneal, or Fallopian Tube Cancer | Recurrent or Refractory Ovarian, Primary Peritoneal, or Fallopian Tube Cancer | NY-ESO-1 | Roswell Park Cancer Institute | NY, USA | |
NCT04318964 | TAEST16001 in the Treatment of Soft Tissue Sarcoma | Soft Tissue Sarcoma | NY-ESO-1, LAGE-1 | Sun Yat-sen University | Guangzhou, China | |
NCT03247309 | TCR-engineered T Cells in Solid Tumors (ACTengine IMA201-101) | Solid Tumor, Recurrent Solid Tumors, Refractory Solid Tumors | MAGEA4/A8 | Immatics US, Inc. | TX, USA | |
NCT01333046 | Administration of TAA-Specific CTLs; Hodgkin or Non-Hodgkin Lymphoma; TACTAL | Hodgkin Lymphoma, Non-Hodgkin Lymphom, |Hodgkin Disease | NY-ESO-1, MAGEA4, PRAME, SSX. | Baylor College of Medicine | TX, USA | |
NCT03441100 | TCR-engineered T Cells in Solid Tumors: IMA202-101 | Solid Tumor, Recurrent Solid Tumors, Refractory Solid Tumors | MAGEA1 | Immatics US, Inc. | TX, USA | |
NCT03450122 | Modified T Cells, Chemotherapy, and Aldesleukin With or Without LV305 and CMB305 in Treating Participants With Advanced or Recurrent Sarcoma | Advanced or Recurrent Sarcoma | NY-ESO-1 | M.D. Anderson Cancer Center | TX, USA | |
NCT04679194 | Study of Mana 312 (Multi Tumor-Associated Antigen T Cells) in Adults With AML/MDS After HSCT | AML/MDS | WT1, PRAME | Mana Therapeutics | VA, USA | |
NCT03250325 | Study of TBI-1301 (NY-ESO-1 T Cell Receptor Gene Transduced Autologous T Lymphocytes) in Patients With Synovial Sarcoma | Synovial Sarcoma | NY-ESO-1 | Takara Bio Inc. | CA, USA | |
NCT02475707 | Administration of Donor MultiTAA-Specific T Cells for ALL (STELLA) | Leukemia, Lymphoblastic (Acute) | WT1, NY-ESO-1, PRAME | Baylor College of Medicine | TX, USA | |
Vaccine | NCT02737787 | A Phase I Study of WT1 or NY-ESO-1 Vaccine and Nivolumab For Recurrent Ovarian Cancer | Ovarian, Fallopian Tube, Primary Peritoneal Cancer, Recurrent Ovarian Cancer | WT1, NY-ESO-1 | Memorial Sloan Kettering Cancer Center | NY, USA |
NCT01697527 | Gene and Vaccine Therapy in Treating Patients With Advanced Malignancies | Malignant Neoplasm | NY-ESO-1 | Jonsson Comprehensive Cancer Center | CA, USA | |
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Nin, D.S.; Deng, L.-W. Biology of Cancer-Testis Antigens and Their Therapeutic Implications in Cancer. Cells 2023, 12, 926. https://doi.org/10.3390/cells12060926
Nin DS, Deng L-W. Biology of Cancer-Testis Antigens and Their Therapeutic Implications in Cancer. Cells. 2023; 12(6):926. https://doi.org/10.3390/cells12060926
Chicago/Turabian StyleNin, Dawn Sijin, and Lih-Wen Deng. 2023. "Biology of Cancer-Testis Antigens and Their Therapeutic Implications in Cancer" Cells 12, no. 6: 926. https://doi.org/10.3390/cells12060926